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Thymosin β(10) Expression Driven by the Human TERT Promoter Induces Ovarian Cancer-Specific Apoptosis through ROS Production
Thymosin β(10) (Tβ(10)) regulates actin dynamics as a cytoplasm G-actin sequestering protein. Previously, we have shown that Tβ(10) diminishes tumor growth, angiogenesis, and proliferation by disrupting actin and by inhibiting Ras. However, little is known about its mechanism of action and biologica...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356296/ https://www.ncbi.nlm.nih.gov/pubmed/22623951 http://dx.doi.org/10.1371/journal.pone.0035399 |
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author | Kim, Young-Chae Kim, Byoung-Gie Lee, Je-Ho |
author_facet | Kim, Young-Chae Kim, Byoung-Gie Lee, Je-Ho |
author_sort | Kim, Young-Chae |
collection | PubMed |
description | Thymosin β(10) (Tβ(10)) regulates actin dynamics as a cytoplasm G-actin sequestering protein. Previously, we have shown that Tβ(10) diminishes tumor growth, angiogenesis, and proliferation by disrupting actin and by inhibiting Ras. However, little is known about its mechanism of action and biological function. In the present study, we establish a new gene therapy model using a genetically modified adenovirus, referred to as Ad.TERT.Tβ(10), that can overexpress the Tβ(10) gene in cancer cells. This was accomplished by replacing the native Tβ(10) gene promoter with the human TERT promoter in Ad.TERT.Tβ(10). We investigated the cancer suppression activity of Tβ(10) and found that Ad.TERT.Tβ(10) strikingly induced cancer-specific expression of Tβ(10) as well as apoptosis in a co-culture model of human primary ovarian cancer cells and normal fibroblasts. Additionally, Ad.TERT.Tβ(10) decreased mitochondrial membrane potential and increased reactive oxygen species (ROS) production. These effects were amplified by co-treatment with anticancer drugs, such as paclitaxel and cisplatin. These findings indicate that the rise in ROS production due to actin disruption by Tβ(10) overexpression increases apoptosis of human ovarian cancer cells. Indeed, the cancer-specific overexpression of Tβ(10) by Ad.TERT.Tβ(10) could be a valuable anti-cancer therapeutic for the treatment of ovarian cancer without toxicity to normal cells. |
format | Online Article Text |
id | pubmed-3356296 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33562962012-05-23 Thymosin β(10) Expression Driven by the Human TERT Promoter Induces Ovarian Cancer-Specific Apoptosis through ROS Production Kim, Young-Chae Kim, Byoung-Gie Lee, Je-Ho PLoS One Research Article Thymosin β(10) (Tβ(10)) regulates actin dynamics as a cytoplasm G-actin sequestering protein. Previously, we have shown that Tβ(10) diminishes tumor growth, angiogenesis, and proliferation by disrupting actin and by inhibiting Ras. However, little is known about its mechanism of action and biological function. In the present study, we establish a new gene therapy model using a genetically modified adenovirus, referred to as Ad.TERT.Tβ(10), that can overexpress the Tβ(10) gene in cancer cells. This was accomplished by replacing the native Tβ(10) gene promoter with the human TERT promoter in Ad.TERT.Tβ(10). We investigated the cancer suppression activity of Tβ(10) and found that Ad.TERT.Tβ(10) strikingly induced cancer-specific expression of Tβ(10) as well as apoptosis in a co-culture model of human primary ovarian cancer cells and normal fibroblasts. Additionally, Ad.TERT.Tβ(10) decreased mitochondrial membrane potential and increased reactive oxygen species (ROS) production. These effects were amplified by co-treatment with anticancer drugs, such as paclitaxel and cisplatin. These findings indicate that the rise in ROS production due to actin disruption by Tβ(10) overexpression increases apoptosis of human ovarian cancer cells. Indeed, the cancer-specific overexpression of Tβ(10) by Ad.TERT.Tβ(10) could be a valuable anti-cancer therapeutic for the treatment of ovarian cancer without toxicity to normal cells. Public Library of Science 2012-05-18 /pmc/articles/PMC3356296/ /pubmed/22623951 http://dx.doi.org/10.1371/journal.pone.0035399 Text en Kim et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Kim, Young-Chae Kim, Byoung-Gie Lee, Je-Ho Thymosin β(10) Expression Driven by the Human TERT Promoter Induces Ovarian Cancer-Specific Apoptosis through ROS Production |
title | Thymosin β(10) Expression Driven by the Human TERT Promoter Induces Ovarian Cancer-Specific Apoptosis through ROS Production |
title_full | Thymosin β(10) Expression Driven by the Human TERT Promoter Induces Ovarian Cancer-Specific Apoptosis through ROS Production |
title_fullStr | Thymosin β(10) Expression Driven by the Human TERT Promoter Induces Ovarian Cancer-Specific Apoptosis through ROS Production |
title_full_unstemmed | Thymosin β(10) Expression Driven by the Human TERT Promoter Induces Ovarian Cancer-Specific Apoptosis through ROS Production |
title_short | Thymosin β(10) Expression Driven by the Human TERT Promoter Induces Ovarian Cancer-Specific Apoptosis through ROS Production |
title_sort | thymosin β(10) expression driven by the human tert promoter induces ovarian cancer-specific apoptosis through ros production |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356296/ https://www.ncbi.nlm.nih.gov/pubmed/22623951 http://dx.doi.org/10.1371/journal.pone.0035399 |
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